Engineering molecular nanoprobes to target early atherosclerosis: Precise diagnostic tools and promising therapeutic carriers

Abstract

Atherosclerosis, an inflammation-driven chronic blood vessel disease, is a major contributor to devastating cardiovascular events, bringing serious social and economic burdens. Currently, non-invasive diagnostic and therapeutic techniques in combination with novel nanosized materials as well as established molecular targets are under active investigation to develop integrated molecular imaging approaches, precisely visualizing and/or even effectively reversing early-stage plaques. Besides, mechanistic investigation in the past decades provides many potent candidates extensively involved in the initiation and progression of atherosclerosis. Recent hotly-studied imaging nanoprobes for detecting early plaques mainly including optical nanoprobes, photoacoustic nanoprobes, magnetic resonance nanoprobes, positron emission tomography nanoprobes, and other dual- and multi-modality imaging nanoprobes, have been proven to be surface functionalized with important molecular targets, which occupy tailored physical and biological properties for atherogenesis. Of note, these engineering nanoprobes provide long blood-pool residence and specific molecular targeting, which allows efficient recognition of early-stage atherosclerotic plaques and thereby function as a novel type of precise diagnostic tools as well as potential therapeutic carriers of anti-atherosclerosis drugs. There have been no available nanoprobes applied in the clinics so far, although many newly emerged nanoprobes, as exemplified by aggregation-induced emission nanoprobes and TiO₂ nanoprobes, have been tested for cell lines in vitro and atherogenic animal models in vivo, achieving good experimental effects. Therefore, there is an urgent call to translate these preclinical results for nanoprobes into clinical trials. For this reason, this review aims to give an overview of currently investigated nanoprobes in the context of atherosclerosis, summarize relevant published studies showing applications of different kinds of formulated nanoprobes in early detection and reverse of plaques, discuss recent advances and some limitations thereof, and provide some insights into the development of the new generation of more precise and efficient molecular nanoprobes, with a critical property of specifically targeting early atherosclerosis.

Keywords: Atherosclerosis; Dual-modality; Early-stage; Molecular imaging; Multi-modality; Nanoprobes; Precise diagnosis; Single-modality; Therapeutics.

Figure 1

Single-modality imaging nanoprobes for early detection and prevention of atherosclerotic plaques. Depicted are four common types of single-modality imaging nanoprobes applied in atherosclerosis research, including optical imaging nanoprobes, photoacoustic imaging nanoprobes, magnetic resonance imaging nanoprobes, and positron emission tomography imaging nanoprobes. Representative nanoprobes in each category are listed in detail here according to current studies.

Figure 2

Optical and photoacoustic-based dual-modality imaging nanoprobes for early detection and prevention of plaques. Described are three reported types of optical and photoacoustic-based dual-modality imaging nanoprobes applied in current atherosclerotic studies, mainly including optical/MR imaging nanoprobes, optical/ultrasound imaging nanoprobes, and photoacoustic/ ultrasound imaging nanoprobes. Specific molecular targets and biological processes are displayed.